TGI Friday! Our weekly round-up of recently published research abstracts | 21 February 2014

February 21, 2014

From Medical Hypotheses, September 2013.

Chronic fatigue syndrome from vagus nerve infection: a psychoneuroimmunological hypothesis.

Michael B VanElzakker.


Chronic fatigue syndrome (CFS) is an often-debilitating condition of unknown origin. There is a general consensus among CFS researchers that the symptoms seem to reflect an ongoing immune response, perhaps due to viral infection. Thus, most CFS research has focused upon trying to uncover that putative immune system dysfunction or specific pathogenic agent. However, no single causative agent has been found.

In this speculative article, I describe a new hypothesis for the etiology of CFS: infection of the vagus nerve. When immune cells of otherwise healthy individuals detect any peripheral infection, they release proinflammatory cytokines. Chemoreceptors of the sensory vagus nerve detect these localized proinflammatory cytokines, and send a signal to the brain to initiate sickness behavior. Sickness behavior is an involuntary response that includes fatigue, fever, myalgia, depression, and other symptoms that overlap with CFS.

The vagus nerve infection hypothesis of CFS contends that CFS symptoms are a pathologically exaggerated version of normal sickness behavior that can occur when sensory vagal ganglia or paraganglia are themselves infected with any virus or bacteria.

Drawing upon relevant findings from the neuropathic pain literature, I explain how pathogen-activated glial cells can bombard the sensory vagus nerve with proinflammatory cytokines and other neuroexcitatory substances, initiating an exaggerated and intractable sickness behavior signal.

According to this hypothesis, any pathogenic infection of the vagus nerve can cause CFS, which resolves the ongoing controversy about finding a single pathogen. The vagus nerve infection hypothesis offers testable hypotheses for researchers, animal models, and specific treatment strategies.

From Fatigue., 1 January 2014.

Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis.

Jason LA(1), Sunnquist M(1), Brown A(1), Evans M(1), Vernon SD(2), Furst J(3), Simonis V(3).
1) Center for Community Research, DePaul University, Chicago, IL USA.
2) The CFIDS Association of America.
3) College of Computing and Digital Media, DePaul University, Chicago, USA.



Considerable controversy has transpired regarding the core features of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS).

Current case definitions differ in the number and types of symptoms required.

This ambiguity impedes the search for biological markers and effective treatments.


This study sought to empirically operationalize symptom criteria and identify which symptoms best characterize the illness.


Patients (n=236) and controls (n=86) completed the DePaul Symptom Questionnaire, rating the frequency and severity of 54 symptoms.

Responses were compared to determine the threshold of frequency/severity ratings that best distinguished patients from controls.

A Classification and Regression Tree (CART) algorithm was used to identify the combination of symptoms that most accurately classified patients and controls.


A third of controls met the symptom criteria of a common CFS case definition when just symptom presence was required; however, when frequency/severity requirements were raised, only 5% met criteria.

Employing these higher frequency/severity requirements, the CART algorithm identified three symptoms that accurately classified 95.4% of participants as patient or control:

fatigue/extreme tiredness, inability to focus on multiple things simultaneously, and experiencing a dead/heavy feeling after starting to exercise.


Minimum frequency/severity thresholds should be specified in symptom criteria to reduce the likelihood of misclassification.

Future research should continue to seek empirical support of the core symptoms of ME and CFS to further progress the search for biological markers and treatments.

From The Journal of Sports Medicine and Physical Fitness, April 2014.

Influence of graded exercise therapy on anxiety levels and health-related quality of life in chronic fatigue syndrome

Klasnja A(1), Grujic N(1), Popadic Gacesa J(1), Barak O(1), Tomic S(2,3), Brkic S(2,3)
1) Department of Physiology, Medical faculty University of Novi Sad, Novi Sad, Serbia;
2) Clinic for Infectious Diseases Clinical Center Vojvodina, Vojvodina, Serbia;
3) Medical Faculty, University of Novi Sad Novi Sad, Serbia



The purpose of the present study was twofold: 1) to determine to what extent graded exercise therapy (GET) improves health-related quality of life (HRQOL) and anxiety levels in patients with chronic fatigue syndrome (CFS); and 2) to correlate scores of HRQOL and anxiety levels in CFS patients.


Anxiety and HRQOL were assessed in 26 CFS patients before and after 12 weeks of GET. Anxiety was measured using the State-Trait Anxiety Inventory questionnaire (STAI) and HRQOL using the Medical Outcomes Study Short-Form questionnaire (SF-36).


GET significantly decreased trait anxiety (STAI-T) levels in patients with CFS. Patients' scores on SF-36 following GET showed higher levels of functioning, but only the ‘vitality' subscale scores showed a statistically significant difference. A negative correlation was present between all eight subscales of SF-36 and anxiety levels. The strongest negative correlation for both state and trait anxiety scores (STAI-S and STAI-T) was found with the scores on the ‘Limitations due to emotional problems' subscale of SF-36 (r=-0.69 and r=-0.55, respectively), while the weakest negative correlation was with the ‘Physical functioning' subscale scores (r=-0.30 and r=-0.31, respectively).


Graded exercise therapy has a positive effect on both physical and psychological state of CFS patients. GET can decrease anxiety and improve quality of life of CFS patients. CFS patients with higher state and trait anxiety levels have lower quality of life, and vice versa.

From Pain Practice, 17 February 2014 (published ahead of print).

Endogenous Pain Modulation in Response to Exercise in Patients with Rheumatoid Arthritis, Patients with Chronic Fatigue Syndrome and Comorbid Fibromyalgia, and Healthy Controls: A Double-Blind Randomized Controlled Trial.

Mira Meeus PhD, PT(1,2,3,4,*), Linda Hermans PT(3,4), Kelly Ickmans PT(1,2,4), Filip Struyf PT(2,4), Deborah Van Cauwenbergh PT(2,4), Laura Bronckaerts PT(1), Luc S. De Clerck PhD, MD(5), Greta Moorken PhD, MD(4,6), Guy Hans PhD, MD(7), Sofie Grosemans FN(7), Jo Nijs PhD, PT(1,4,8)
1) Departments of Human Physiology and Rehabilitation Sciences, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium
2) Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
3) Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
4) “Pain in Motion” Research Group
5) Department of Immunology, Allergy and Rheumatology, University of Antwerp (UA), Antwerp, Belgium
6) Department of Internal Medicine, University Hospital Antwerp (UZA), Antwerp, Belgium
7) Multidisciplinary Pain Center (PCT), University Hospital Antwerp (UZA), Antwerp, Belgium
8) Department of Rehabilitation and Physiotherapy, University Hospital Brussels, Brussels, Belgium



Temporal summation (TS) of pain, conditioned pain modulation (CPM), and exercise-induced analgesia (EIA) are often investigated in chronic pain populations as an indicator for enhanced pain facilitation and impaired endogenous pain inhibition, respectively, but interactions are not yet clear both in healthy controls and in chronic pain patients. Therefore, the present double-blind randomized placebo-controlled study evaluates pains
cores, TS, and CPM in response to exercise in healthy controls, patients with chronic fatigue syndrome and comorbid fibromyalgia (CFS/FM), and patients with rheumatoid arthritis (RA), both under placebo and paracetamol condition.


Fifty-three female volunteers – of which 19 patients with CFS/FM, 16 patients with RA, and 18 healthy controls – underwent a submaximal exercise test on a bicycle ergometer on 2 different occasions (paracetamol vs. placebo), with an interval of 7 days. Before and after exercise, participants rated pain intensity during TS
and CPM.


Patients with rheumatoid arthritis showed decreased TS after exercise, both after paracetamol and placebo (P < 0.05). In patients with CFS/FM, results were less univocal. A nonsignificant decrease in TS was only observed after taking paracetamol. CPM responses to exercise are inconclusive, but seem to worsen after exercise. No adverse effects were seen.CONCLUSIONThis study evaluates pain scores, TS, and CPM in response to submaximal exercise in 2 different chronic pain populations and healthy controls. In patients with RA, exercise had positive effects on TS, suggesting normal EIA. In patients with CFS/FM, these positive effects were only observed after paracetamol and results were inconsistent.

From The New Microbiologica, 15 January 2014.

No evidence of XMRV provirus sequences in patients with myalgic encephalomyelitis/chronic fatigue syndrome and individuals with unspecified encephalopathy

Santa Rasa(1,*), Zaiga Nora-Krukle(1), Svetlana Chapenko(1), Angelika Krumina(2), Silvija Roga(3), Modra Murovska(1)
1) August Kirchenstein Institute of Microbiology and Virology, Riga Stradins University, Latvia;
2) Department of Infectology and Dermatology, Riga Stradins University, Latvia;
3) Department of Pathology, Riga Stradins University, Latvia
* Corresponding author. August Kirchenstein Institute of Microbiology and Virology, Riga Stradins University, Ratsupites Street 5, LV-1067, Riga, Latvia. E-mail:


Xenotropic murine leukemia virus-related virus (XMRV) has been considered a possible trigger of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) and could also be linked with unspecified encephalopathy. The aim of this study was to analyse the frequency of XMRV proviral sequences in peripheral blood leukocyte (PBL) DNA from 150 patients with ME/CFS and 30 apparently healthy individuals, as well as in PBL and brain tissue DNA from 61 individuals with/without unspecified encephalopathy.

Targeting the XMRV proviral gag gene sequence by nested polymerase chain reaction (nPCR) with previously reported primer sets, provirus was not detected either in DNA from patients with ME/CFS and individuals with unspecified encephalopathy, or in apparently healthy individuals. Only the positive control gave the amplimer of 410 base pairs (bp) after the second round that corresponds to the expected XMRV gag gene fragment. In addition, DNA was found to be negative in nPCR assays, targeting XMRV specific env gene sequence, using previously described primer sets. Also only positive control gave the amplimer of 218 bp after the second round, corresponding to the expected XMRV env gene fragment.

Using nPCR we found no evidence of XMRV infection either in apparently healthy individuals or in patients with ME/CFS and individuals with unspecified encephalopathy.


2 thoughts on “TGI Friday! Our weekly round-up of recently published research abstracts | 21 February 2014”

  1. Very interested in the Vagus Nerve/infection hypothesis. The Wikipedia information on the Vagus Nerve describes just how far reaching and indispensable this part of our anatomy is. Dysfunction of this nerve can disrupt the most basic operations of a huge number of physical and cognitive capabilities. Would like to see a lot more research for the benefit of patients in this area.

  2. I fail to see how vagus nerve infection could cause the immediate build-up of lactic acid in muscles when put under any extra strain, (such as encountering a slight rise in incline of the pavement).

    Why this neverending use of the word fatigue?
    We don’t all get “fatigue” or “feel tired”.
    Our bodies simply won’t make enough energy for us to be able to do anything. Aerobic metabolism doesn’t happen.

    And why report on any “CFS” studies at all? This is the MEAssociation!

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